This proposal is part of a continued effort to examine the role of inflammatory cells and mediators in the airway injury produced by inhalation of environmental and occupational agents. This research proposal will examine the acute and subchronic pulmonary effects of machining fluid aerosols - an occupational hazard for nearly 1 million workers in this country. Machining fluids/cutting oils are hypoosmolar, alkaline fluids which are frequently contaminated with a variety of microbial agents. The major goals of the proposed studies are to 1) determine the roles of contaminating endotoxin, hypotonicity, and alkalinity in the adverse pulmonary effects associated with occupational exposure to machining fluid aerosols; and 2) compare the potential of different classes of machining fluids to produce inflammatory and functional changes in the lung. Adverse pulmonary effects after single and repeated exposures to machining fluid aerosols will be examined using functional, biochemical, and morphological techniques in a sensitive guinea pig model. Thus, the proposed studies will determine whether subclinical inflammatory changes persist in the lung after repeated exposure to machining fluid aerosols at exposure concentrations near the current TLV. The proposed experiments will help to provide a clearer understanding of the role of microbial contamination in the pulmonary effects of inhaled machining fluid aerosols.